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Additional file 1: Table S1. Encapsulation efficiency stability of the drug in 4 liposomes at 3 months (n = 3). Fig. S1. Diameter and ζ-potential of Tf-ELE/CTX@BLIP, Tf-ELE/CTX@LIP, ELE/CTX@BLIP and ELE/CTX@LIP. Fig. S2. 7-days stability of TF-ELE/CTX@BLIP diameter in different medium. Fig. S3. Flow cytometry analysis of RG2 glioma cells after incubation with Tf-ELE/CTX@BLIP, Tf-ELE/CTX@LIP, ELE/CTX@BLIP and ELE/CTX@LIP for 2 h. Rho B = 20 μg/mL. Fig. S4. CLSM images of RG2, U251 and C6 glioma cells treated with Tf-ELE/CTX@BLIP for 2 h. Scale bar = 50 μm. Fig. S5. Flow cytometry analysis of RAW264.7 cells treated with Tf-ELE/CTX@BLIP, Tf-ELE/CTX@LIP, ELE/CTX@BLIP and ELE/CTX@LIP for 2 h. Rho B = 20 μg/mL. Fig. S6. WB analysis of P-gp in bEnd.3 cells. Relative protein expression was calculated. Cells preconditioned with (1) control; (2) verapamil; (3) ELE/CTX@LIP; (4) ELE/CTX@BLIP; (5) Tf-ELE/CTX@LIP; (6) Tf-ELE/CTX@BLIP. (*P < 0.05, n=3). Fig. S7. Corresponding quantitative fluorescent analysis of brain, liver, heart, spleen, lung and kidney at 48 h post-injection in glioma-beard mice. *p < 0.05. Fig. S8. In vivo fluorescence imaging of Tf-Cypate@BLIP, Tf-Cypate@LIP, Cypate@BLIP and Cypate@LIP in normal mice. Cypate = 0.5 mg/kg. Fig. S9. Averaged fluorescent intensity of saline, free CTX, free ELE, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP and Tf-ELE/CTX@BLIP in nude mice bearing orthotopic glioma brain within 15 days of treatments. Fig. S10. H&E staining of brain sections of orthotopic glioma-bearing mice in different formulation groups. Fig. S11. Biochemical parameter analysis after treated with saline, free CTX, free ELE, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP and Tf-ELE/CTX@BLIP. (A) BLI-T: total bilirubin, (B) BUN: blood urea nitrogen, (C) URIC: uric acid, (D) ALT: alanine transaminase, (E) CRE: creatinine, (F) AST: aspartate transaminase.

Jie Li,1– 4 Jiaqian Zhao,2– 5 Tiantian Tan,2– 4 Mengmeng Liu,2– 4 Zhaowu Zeng,2– 4 Yiying Zeng,2– 4 Lele Zhang,6 Chaomei Fu,1 Dajing Chen,2– 4 Tian Xie2– 4 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Holistic Integrative Pharmacy Institutes, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 3Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 4Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 5College of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 6School of Medicine, Chengdu University, Chengdu, People’s Republic of ChinaCorrespondence: Tian Xie; Zhaowu ZengHolistic Integrative Pharmacy Institutes, Hangzhou Normal University, 1378 Wenyixi Road, Hangzhou, Zhejiang 311121, People’s Republic of ChinaTel +86 5 712 886 8269Email xbs@dljg.sina.net; artgreenking@126.comAbstract: Gliomas are the most common tumor of the central nervous system. However, the presence of the brain barrier blocks the effective delivery of drugs and leads to the treatment failure of various drugs. The development of a nanoparticle drug delivery system (NDDS) can solve this problem. In this review, we summarized the brain barrier (including blood–brain barrier (BBB), blood–brain tumor barriers (BBTB), brain–cerebrospinal fluid barrier (BCB), and nose-to-brain barrier), NDDS of glioma (such as passive targeting systems, active targeting systems, and environmental responsive targeting systems), and NDDS efficacy improvement strategies and deficiencies. The research prospect of drug-targeted delivery systems for glioma is also discussed.Keywords: glioma, brain barrier, nanoparticle drug delivery system, efficacy improvement strategies, deficiencies of NDDS

Bingtao Zhai,1 Yiying Zeng,2–5 Zhaowu Zeng,2–4 Nana Zhang,2–4 Chenxi Li,2–4 Yijun Zeng,2–4 Yu You,1 Shuling Wang,2–4 Xiabin Chen,2–4 Xinbing Sui,2–4 Tian Xie2–4 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; 2Holistic Integrative Pharmacy Institutes, Hangzhou Normal University, Hangzhou, Zhejiang, China; 3Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou, Zhejiang, China; 4Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou, Zhejiang, China; 5College of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China Abstract: β-elemene is a noncytotoxic Class II antitumor drug extracted from the traditional Chinese medicine Curcuma wenyujin Y. H. Chen et C. Ling. β-elemene exerts its effects by inhibiting cell proliferation, arresting the cell cycle, inducing cell apoptosis, exerting antiangiogenesis and antimetastasis effects, reversing multiple-drug resistance (MDR), and enhancing the immune system. Elemene injection and oral emulsion have been used to treat various tumors, including cancer of the lung, liver, brain, breast, ovary, gastric, prostate, and other tissues, for >20years. The safety of both elemene injection and oral emulsion in the clinic has been discussed. Recently, the secondary development of β-elemene has attracted the attention of researchers and made great progress. On the one hand, studies have been carried out on liposome-based systems (including solid lipid nanoparticles [SLNs], nanostructured lipid carriers [NLCs], long-circulating liposomes, active targeting liposomes, and multidrug-loaded liposomes) and emulsion systems (including microemulsions, self-emulsion drug delivery systems [SEDDSs], and active targeting microemulsion) to solve the issues of poor solubility in water, low bioavailability, and severe phlebitis, as well as to improve antitumor efficacy. The pharmacokinetics of different drug delivery systems of β-elemene are also summarized. On the other hand, a number of highly active anticancer β-elemene derivatives have been obtained through modification of the structure of β-elemene. This review focuses on the two drug delivery systems and derivatives of β-elemene for cancer therapy. Keywords: β-elemene, pharmacokinetics, drug delivery system, derivative, safety

A new amylase gene APGA1 was cloned from Aureobasidium pullulans NRRL 12974 and expressed in Pichia pastoris . This is the first report on cloning and expression of amylolytic gene from the industrially important microorganism A. pullulans . The purified recombinant protein with MW of 66 kDa and specific activity of 298.02 Umg -1 protein was verified as a glucoamylase by its hydrolytic mode. This recombinant glucoamylase with optimal pH of 4.5, and temperature of 60°C, showed good hydrolytic activity against raw potato starch. At 60°C, 83.1% of raw potato starch slurry (150 gl -1 ) was hydrolysed into glucose by 0.1 U mg -1 starch purified recombinant glucoamylase in less than 2.5 h. This is the highest raw starch hydrolysis efficiency report about recombinant fungal glucoamylase. This useful property indicated that this glucoamylase may find important applications in the starch saccharification industry and in bioethanol production. Key words: Glucoamylase, Aureobasidium pullulans, expression, raw starch degradation.

Rongrong Wang,1 Renzhong Xiao,2 Zhaowu Zeng,2 Lili Xu,2 Junjie Wang21Campus Hospital of Zhejiang University, 2Research Center for Biomedicine and Health, Hangzhou Normal University, Hangzhou, ChinaAbstract: Poly(ethylene glycol)–distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers are biocompatible and amphiphilic polymers that can be widely utilized in the preparation of liposomes, polymeric nanoparticles, polymer hybrid nanoparticles, solid lipid nanoparticles, lipid–polymer hybrid nanoparticles, and microemulsions. Particularly, the terminal groups of PEG can be activated and linked to various targeting ligands, which can prolong the circulation time, improve the drug bioavailability, reduce undesirable side effects, and especially target specific cells, tissues, and even the intracellular localization in organelles. This review herein aims to describe recent developments in drug carriers exploiting PEG-DSPE block copolymers and their derivatives, and the incorporation of different ligands to the end groups of PEG-DSPE to target delivery, focusing on their modification approaches, advantages, applications, and the probable associated drawbacks.Keywords: PEG-DSPE, PEG-lipid, Mal-PEG-DSPE, targeting delivery

Jun Jie Wang1, Zhao Wu Zeng1,2, Ren Zhong Xiao1, Tian Xie1, Guang Lin Zhou1, Xiao Ri Zhan1, Shu Ling Wang11Research Center for Biomedicine and Health, Hangzhou Normal University, Hangzhou, Zhejiang, People's Republic of China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People's Republic of ChinaAbstract: Chitosan nanoparticles are good drug carriers because of their good biocompatibility and biodegradability, and can be readily modified. As a new drug delivery system, they have attracted increasing attention for their wide applications in, for example, loading protein drugs, gene drugs, and anticancer chemical drugs, and via various routes of administration including oral, nasal, intravenous, and ocular. This paper reviews published research on chitosan nanoparticles, including its preparation methods, characteristics, modification, in vivo metabolic processes, and applications.Keywords: chitosan nanoparticle, drug delivery system, preparation, modification, application

Ren Zhong Xiao1, Zhao Wu Zeng1,2, Guang Lin Zhou1, Jun Jie Wang1, Fan Zhu Li2, An Ming Wang11Research Center for Biomedicine and Health, Hangzhou Normal University, Hangzhou, Zhejiang, China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaAbstract: Due to their small particle size and large and modifiable surface, nanoparticles have unique advantages compared with other drug carriers. As a research focus in recent years, polyethylene glycol–polylactic acid (PEG–PLA) block copolymer and its end-group derivative nanoparticles can enhance the drug loading of hydrophobic drugs, reduce the burst effect, avoid being engulfed by phagocytes, increase the circulation time of drugs in blood, and improve bioavailability. Additionally, due to their smaller particle size and modified surface, these nanoparticles can accumulate in inflammation or target locations to enhance drug efficacy and reduce toxicity. Recent advances in PEG–PLA block copolymer nanoparticles, including the synthesis of PEG–PLA and the preparation of PEG–PLA nanoparticles, were introduced in this study, in particular the drug release and modifiable characteristics of PEG–PLA nanoparticles and their application in pharmaceutical preparations.Keywords: PEG–PLA, block copolymer, nanoparticles, drug delivery system